Several functional markers of the immune system may be used either as markers of successful aging or conversely as markers of unsuccessful aging. Particularly, a combination of high CD8 and low CD4 and poor T cell proliferation has been associated with a higher two-year mortality in very old subjects. Therefore, ...

Inflammation is a human being's primary defense against threats to homeostasis that are encountered every day. Especially in old age, when regulatory mechanisms responsible for inflammatory responses may be ineffective or damaged, the result can be adverse pathological conditions, and an increased risk of morbidity and mortality. The inflammation response ...

Long-term culture studies using CD8 T cells, the immune cells responsible for control of viral infection, have identified the major features of replicative senescence. Aging is associated with increased proportions of CD8 T cells with similar characteristics, such as absence of expression of the CD28 costimulatory molecule and reduced antiviral ...

It is generally accepted that aging is a phenomenon of irreversibility, inevitability, and universality with parenchymal loss and functional decline. Consequently, the major goals of aging research are focused on the development of a replace strategy of the aged organs or cells, based on immortalizing tools, stem cells, or artificial ...

Werner syndrome (WS) fibroblasts enter replicative senescence after a reduced in vitro life span. Although this has been postulated as causal in the accelerated aging seen in this disease, controversy remains as to whether WS is showing the acceleration of a normal cellular aging mechanism or, instead, the occurrence of ...

The ability to track antigen (Ag)-specific lymphocyte populations in vivo has greatly increased our understanding of the location and functional status of these cells throughout the course of an immune response. Recent technical advances have enhanced researchers' capability to follow migration, activation and cellular interactions of Ag-specific lymphocytes in situ. ...

Solanum nigrum L. (SNL) has been traditionally used as an herbal plant for a long time. In the present study, SNL glycoprotein showed a dose-dependent radical scavenging activity on radicals, including 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals, hydroxyl radical (OH), and superoxide anion (O(2)(-)). When the HT-29 cells were treated with 60μg/ml SNL ...

Age-related decreases in immune function are thought to contribute to the reduced efficacy of vaccinations seen in elderly populations. Our previous in vitro studies demonstrated that naive CD4 T cells from aged TCR-transgenic mice proliferate less than young cells and generate poorly functioning effectors due to decreased IL-2 production. In ...

Ageing is accompanied by 2-4-fold increases in plasma/serum levels of inflammatory mediators such as cytokines and acute phase proteins. A wide range of factors seems to contribute to this low-grade inflammation, including an increased amount of fat tissue, decreased production of sex steroids, smoking, subclinical infections (e.g. asymptomatic bacteriuria), and ...

The innate immune system serves an important role in preventing microbial invasion. However, it experiences significant changes with advancing age. Among the age-associated changes are: Aged macrophages and neutrophils have impaired respiratory burst and reactive nitrogen intermediates as a result of altered intracellular signaling, rendering them less able to destroy ...

To interfere with host immune responses, some microbial pathogens produce proteins with the properties of superantigens, which can interact via conserved V region framework subdomains of the Ag receptors of lymphocytes rather than the complementarity-determining region involved in the binding of conventional Ags. In recent studies, we have elucidated how ...

Long-lived clonal T cells deficient in CD28 expression are commonly found in patients with inflammatory syndromes and persistent infections. Considering that CD28 loss is the most consistent immunological marker of aging, we propose that, in pathological states, CD28(null) T cells represent prematurely senescent cells resulting from persistent immune activation. These ...

Granulomas are innate sequestration responses that can be modified by superimposed acquired immune mechanisms. The present study examined the innate stage of pulmonary granuloma responses to bead-immobilized Th1- and Th2-inducing pathogen antigens (Ags), Mycobacteria bovis purified protein derivative (PPD) and Schistosoma mansoni soluble egg Ags (SEA). Compared to a nonpathogen ...

During the past years, yeast has been successfully established as a model to study mechanisms of apoptotic regulation. However, the beneficial effects of such a cell suicide program for a unicellular organism remained obscure. Here, we demonstrate that chronologically aged yeast cultures die exhibiting typical markers of apoptosis, accumulate oxygen ...

Elevated levels of homocysteine (Hcy) have been identified as independent risk identifiers for cardiovascular disease, cerebrovascular disease as well as for all-cause mortality. Despite the potential importance of these observations, a definitive pathological role for Hcy or its various metabolites in any of these conditions has not been established. Particularly ...

Recent studies on animal and human autoimmune hemolytic anaemia (AIHA) suggest that the loss of immunological tolerance vs. erythrocyte (Er) self antigens (Ag) may be primed by different mechanisms: ignorance of Er self Ag, molecular mimicry between self and non-self Ag, polyclonal T and/or B cells activation, errors in central ...

Aging and HIV disease show certain immunological similarities. In both situations, control over viral infection is diminished, and there is an increase in certain types of cancer. The immune cell type responsible for controlling viral infections and cancer is the so-called CD8 or cytotoxic T cell. In elderly persons and ...

Vaccination against cancer or intracellular pathogens requires stimulation of class I-restricted CD8(+) T cells. It is therefore important to develop Ag delivery vectors that will promote cross-presentation by APCs and stimulate appropriate inflammatory responses. Toward this goal, we tested the potential of Escherichia coli as an Ag delivery vector in ...

BACKGROUND: Induction of an effective antibody (Ab) response requires delivery of multiple signals to B cells. Cross-linking of the B cell antigen receptor (BCR), signaling through CD40 and CD80/86 and cytokine signals combine to induce class switching and expression of specific isotypes. These signals are principally derived from activated, antigen ...

SR/CR mice are capable of mounting a highly effective response of leukocytes to large doses of lethal transplantable mouse cancer cells. This response is conferred by a dominant, germline-transmissible mutation independent of sex chromosomes. The resistance can be extended to a broad array of mouse and human cancer cells without ...

The immune system is an important evolutionary invention to battle invaders in young and old organisms. Successful aging in humans who achieve nonagenarian status and beyond depends on how the immune system changes over time. Whether certain immune parameters vary with increased age is influenced by the genotype and lifestyle ...

Thymic atrophy, lymphopenia, and compromised cell- and antibody-mediated responses that cause increased rates of infections of longer duration are the immunological hallmarks of zinc deficiency (ZD) in humans and higher animals. As the deficiency advances, a reprogramming of the immune system occurs, beginning with the activation of the stress axis ...

Advanced glycation end products (AGEs), the senescent macroprotein derivatives that form in increased amounts in diabetes, have been implicated in the pathogenesis of diabetic vascular complications. Indeed, AGEs elicit oxidative stress generation in vascular wall cells through an interaction with their receptor (RAGE), thus playing an important role in vascular ...

With advancing age there is a progressive decline in immune responses although this is not inevitable. The impairment in immunocompetence is noticeable as early as 35-40 years in many individuals. At the same time, some persons even in the 80s may show a vigorous immune system comparable with that of ...

Apoptosis plays a vital role in the elimination of anti-self clones, down regulation of immune responses and the killing of virally infected and malignant cells. There is ample evidence that as we age the immune system not only becomes less potent, but dysregulated which includes apoptotic dependent functions. Reductions in ...

Apoptosis is a complex cell-death process that allows cells to die in a controlled fashion. Our overall health relies to a great extent on the proper balance between the normal removal of damaged or unneeded cells via apoptosis and proliferation of the cells that comprise our body. Increasing evidence suggests ...

A variety of changes are observed in the immune system in both animals and humans with increasing age. There is a decline in the functional capacity of the cell populations that mount generalized and focused immune responses, and decreasing production and response of these cells to regulatory signals and proteins. ...

This paper reviews recent findings on immune ageing. Ageing per se affects mainly cell-mediated immunity: decreases in mature T-cells (CD3+) partly compensated with increases in less mature T-cells (CD2+CD3-) are observed. In addition antigen pressure throughout life induces increases in memory T-cells (CD45R0+) and borderline decreases in CD8+ subsets. Those ...

CONTEXT: Influenza and pneumonia rank among the 5 leading causes of death among persons aged 65 and over. Although immunization has been demonstrated to prevent influenza or reduce its incidence and associated complications among the elderly, it has been largely underutilized. PURPOSE: This study examined the association of attitudes, perceived ...

The phenomenon of hormesis is represented by mild stress-induced stimulation of maintenance and repair pathways, resulting in beneficial effects for cells and organisms. We have reported that repeated mild heat stress (RMHS) has anti-aging hormetic effects on growth and various cellular and biochemical characteristics of human skin fibroblasts undergoing aging ...

While the need for vitamin A for the normal progression of male germ cell differentiation has been known for many years, the molecular mechanisms underlying this requirement are poorly understood. This review will explore the aspects of the effects on spermatogenesis of dietary deprivation of vitamin A, in particular as ...

Folate deprivation induces neurotoxicity that is potentiated by additional nutritional and genetic deficiencies including vitamin E and apolipoprotein E deficiency. These deficiencies collectively induce oxidative damage, cognitive impairment, and compensatory alteration in glutathione generation. Treatment with agents that regulate distinct portions of the methionine cycle, including the S-adenosyl homocysteine hydrolase ...

Gelsolin, a Ca(2+)-dependent actin regulatory protein, was recently suggested to participate in apoptosis regulation. In this study, we found that the level of gelsolin is elevated in senescent human diploid fibroblasts (HDFs) and also in the tissues of old rats, i.e., in the liver, kidney, heart, spleen, stomach, and brain, ...

Age-associated changes in the immune system are responsible for an increased likelihood of infection, autoimmune diseases, and cancer in the elderly. Immunosenescence is characterized by reduced levels of the peripheral naive T cell pool derived from thymus and the loss of immature B lineage cells in the bone marrow. Primary ...

One of the essential functions of dendritic cells is to take up Ags in peripheral tissues and migrate into secondary lymphoid organs to present Ags to lymphocytes for the induction of immune responses. Although many studies have demonstrated that the migration of dendritic cells is closely associated with the development ...

Relatively few studies have been published with regard to modification of apoptosis in normal tissues as a function of ageing. The majority of these studies demonstrated an increase in programmed cell death (PCD) with age. However, opposite results, namely loss of apoptotic control with age, have also been reported. In ...

Premature aging of the skin is a prominent side effect of psoralen photoactivation, a therapy widely and successfully used for different skin disorders. Recently, we demonstrated that treatment of fibroblasts with 8-methoxypsoralen and ultraviolet A irradiation resulted in growth arrest with morphological and functional changes reminiscent of replicative senescence. In ...

Severe injury induces detrimental changes in immune function, often leaving the host highly susceptible to developing life-threatening opportunistic infections. Advances in our understanding of how injury influences host immune responses suggest that injury causes a phenotypic imbalance in the regulation of Th1- and Th2-type immune responses. We report in this ...

PURPOSE: To investigate antigen (Ag) specificity, activation, and effector function of the Ag-specific T cells involved in the development of experimental immune-mediated blepharoconjunctivitis (EC), an experimental conjunctivitis. METHODS: EC was induced in Brown Norway rats by injection of ovalbumin (OVA)-specific T cells followed by OVA challenge with eye drops. Eyes, ...

Cellular and molecular events in young (passage 1-3) and aged (passage 25-30) primary mouse aortic smooth muscle cells (MASMC) were investigated. Immunoblot and immunofluorescence analyses indicated that smooth muscle alpha-actin (SM alpha-actin) levels were significantly reduced with increasing in vitro age. Aged MASMC showed an increased proliferative capacity in response ...

The elderly suffer impairments to their immune system, evidenced by higher susceptibility to infections, cancer, and many diseases believed to be autoimmune in nature. A dysregulated overexpression of many proinflammatory cytokines also occurs with aging, as does the synthesis of enzymes that control expression of inflammatory lipid mediators and reactive ...

BACKGROUND: Vitamin D, a common food additive, has been shown to prevent the induction of experimental autoimmune diseases in mice. A possible immune deviation from T(H)1 to T(H)2 responses has been postulated. Although there is no doubt about the beneficial effects of vitamin D, its role in allergy has not ...

From birth to aging the heart undergoes functional changes reflecting biochemical and ultrastructural modifications which imply apoptosis. This is a physiological process resulting from genetic programs closely associated with development and aging. During development apoptosis eliminates redundant cells leading to heart remodeling, while during aging it eliminates damaged or exhausted ...

Rapid removal of pathogens from the circulation by secondary lymphoid organs is prerequisite for successful control of infection. Blood-borne Ags are trapped mainly in the splenic marginal zone. To identify the cell populations responsible for Ag trapping in the marginal zone, mice were selectively depleted of marginal zone macrophages and ...

Proliferation of T cells is important for the expansion of specific T cell clones during immune responses. In addition, for the establishment of protective immunity against viruses, bacteria, and tumors, the expanded T cells must differentiate into effector T cells. Here we show that effector T cell generation is driven ...

Immunosenescence is an age-associated dysregulation of the immune function, which contributes to increased susceptibility to disease in the elderly. Alveolar macrophages (AM) are known phagocytes that generate reactive oxygen species (ROS) and nitric oxide (NO), essential mediators for host defence. We studied phagocytosis, ROS and NO production in AM obtained ...

Apoptosis, or programmed cell death, may lower the risk of neoplasia by removing genetically damaged or mutated cells. A high rate of apoptosis has been linked to a reduced risk of colorectal adenomas; therefore, it is important to understand factors that impact apoptosis. Antioxidants (e.g., vitamin C) protect cells from ...

Osteosarcoma is a bone-forming cancer predominantly found in children and adolescents more often than in adults. Osteosarcoma of the gnathic apparatus is relatively rare in the young population, and this condition becomes a concern of clinical dentists for predominantly the middle-aged and aging patient groups. Osteosarcomas are invaded by lymphocytes, ...

Although it is widely recognized that essential trace elements are required for the differentiation, activation and performance of numerous functions of immune cells, the specific roles of these inorganic micronutrients in these processes remain largely undefined. New insights about the participation of zinc, iron and copper in the selection, maturation ...

Zinc is an essential trace element for life. Zinc is not only an important nutrient, cofactor of numerous enzymes and transcription factors, but also it acts as an intracellular mediator, similarly to calcium. The recent discovery of its intracellular molecular pathways opens the door to new fields of drug design. ...